Featured Publications
Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early‐Onset Osteoporosis
Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N. Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early‐Onset Osteoporosis. Journal Of Bone And Mineral Research 2020, 37: 1125-1135. PMID: 35340077, PMCID: PMC9177665, DOI: 10.1002/jbmr.4550.Peer-Reviewed Original ResearchConceptsAutosomal recessive hypophosphatemic rickets type 2Diffuse idiopathic skeletal hyperostosisEarly-onset osteoporosisENPP1 variantsHypophosphatemic ricketsENPP1 mutationsFibroblast growth factor 23Case 1Growth factor 23Serum phosphate levelsIdiopathic skeletal hyperostosisPosterior longitudinal ligamentCase 3Spinal ligament ossificationFactor 23Skeletal hyperostosisArterial calcificationLongitudinal ligamentPresumptive diagnosisLigament ossificationSevere ossificationMutational statusType 2Pathogenic lossGenetic testing
2023
Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments
Kato H, Braddock D, Ito N. Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments. Current Osteoporosis Reports 2023, 21: 552-566. PMID: 37530996, PMCID: PMC10543536, DOI: 10.1007/s11914-023-00814-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDiffuse idiopathic skeletal hyperostosisAutosomal recessive hypophosphatemic rickets type 2Idiopathic skeletal hyperostosisSkeletal hyperostosisOPLL patientsGenetic factorsPathogenic variantsFibroblast growth factor 23Growth factor 23Posterior longitudinal ligamentSpinal ligament ossificationRecent FindingsRecent studiesStrong genetic factorImportant new biomarkerDisease courseFactor 23Longitudinal ligamentClinical evaluationPlasma biomarkersClinical trialsLigament ossificationPlasma PPiCalcification disordersPatientsEctopic calcificationIRF8 may be a useful marker for blastic plasmacytoid dendritic cell neoplasm, especially with weak CD123 expression
Tang H, Panse G, Braddock D, Perincheri S, Xu M, McNiff J. IRF8 may be a useful marker for blastic plasmacytoid dendritic cell neoplasm, especially with weak CD123 expression. Journal Of Cutaneous Pathology 2023, 50: 595-600. PMID: 37082914, DOI: 10.1111/cup.14439.Peer-Reviewed Original ResearchConceptsBlastic plasmacytoid dendritic cell neoplasmPlasmacytoid dendritic cell neoplasmDendritic cell neoplasmPunch biopsy specimenBiopsy specimenCell neoplasmsCase of BPDCNUseful markerTumor cellsTCL-1 expressionAtypical mononuclear cellsBone marrow involvementDiffuse dermal infiltrateDendritic cell lineagePotential diagnostic pitfallRegulatory factor 8TCL-1BPDCN casesCD123 expressionMarrow involvementDermal infiltrateCutaneous nodulesMyelodysplastic syndromeSkin nodulesMononuclear cells
2022
Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI)
Theng EH, Brewer CC, Oheim R, Zalewski CK, King KA, Delsmann MM, Rolvien T, Gafni RI, Braddock DT, Jeffrey Kim H, Ferreira CR. Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI). Orphanet Journal Of Rare Diseases 2022, 17: 273. PMID: 35854274, PMCID: PMC9295326, DOI: 10.1186/s13023-022-02410-w.Peer-Reviewed Original ResearchConceptsOssicular chain dysfunctionGeneralized Arterial CalcificationOtitis mediaArterial calcificationPrevalence of HLRecurrent otitis mediaTerms of patientTemporal bone imagingEtiology of HLBasic science laboratoryAuricular calcificationConductive HLHL etiologyOtologic featuresDegree of HLCohort studyOtologic evaluationRadiologic featuresAudiological assessmentAuditory dysfunctionTube placementRecurrent episodesBilateral HLCranial CTLikely multifactorial
2021
Direct targeting of amplified gene loci for proapoptotic anticancer therapy
Kaushik Tiwari M, Colon-Rios DA, Tumu HCR, Liu Y, Quijano E, Krysztofiak A, Chan C, Song E, Braddock DT, Suh HW, Saltzman WM, Rogers FA. Direct targeting of amplified gene loci for proapoptotic anticancer therapy. Nature Biotechnology 2021, 40: 325-334. PMID: 34711990, PMCID: PMC8930417, DOI: 10.1038/s41587-021-01057-5.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksTriplex-forming oligonucleotidesDNA damage responseDouble-strand breaksDrug resistanceGene amplificationP53-independent apoptosisHER2-positive breastOvarian cancer modelHuman tumor xenograftsInduction of apoptosisGenomic lociNumber of drugsCellular functionsDamage responseGene locusProtein productsHER2-positive cancer cellsDriver genesClinical efficacyCombat drug resistanceDNA damageHER2 amplificationTherapeutic strategiesTumor xenograftsPlacenta-derived interferon-stimulated gene 20 controls ZIKA virus infection
Ding J, Aldo P, Roberts CM, Stabach P, Liu H, You Y, Qiu X, Jeong J, Maxwell A, Lindenbach B, Braddock D, Liao A, Mor G. Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection. EMBO Reports 2021, 22: embr202152450. PMID: 34405956, PMCID: PMC8490983, DOI: 10.15252/embr.202152450.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionTrophoblast cellsPotential immune modulatory functionsInterferon-stimulated gene 20Anti-viral treatmentHigh-risk populationImmune modulatory functionsAnti-viral responseZika viral infectionImportance of preventionPregnant womenReplacement therapyViral infectionFetal developmentZika virusViral titersModulatory functionViral replicationInfectionAdverse effectsGene 20PregnancyPlacentaRNA viruses
2020
Response of the ENPP1‐Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice
Ferreira CR, Kavanagh D, Oheim R, Zimmerman K, Stürznickel J, Li X, Stabach P, Rettig RL, Calderone L, MacKichan C, Wang A, Hutchinson HA, Nelson T, Tommasini SM, von Kroge S, Fiedler IA, Lester ER, Moeckel GW, Busse B, Schinke T, Carpenter TO, Levine MA, Horowitz MC, Braddock DT. Response of the ENPP1‐Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice. Journal Of Bone And Mineral Research 2020, 36: 942-955. PMID: 33465815, PMCID: PMC8739051, DOI: 10.1002/jbmr.4254.Peer-Reviewed Original ResearchConceptsBone mineral densityLow bone mineral densityTrabecular bone massBone massEarly-onset osteoporosisAsj/Conventional therapyLower trabecular bone massGreater bone fragilityRisk of nephrocalcinosisHigh-phosphate dietLow bone massCortical bone massDevelopment of nephrocalcinosisBone biomechanical propertiesAcademic medical centerPlasma phosphorus concentrationsAutosomal recessive hypophosphatemic ricketsRecessive hypophosphatemic ricketsENPP1 deficiencyRachitic phenotypeMedullary nephrocalcinosisRenal failureNormal chowMineral densityMusculoskeletal Comorbidities and Quality of Life in ENPP1‐Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models
Ferreira CR, Ansh AJ, Nester C, O'Brien C, Stabach PR, Murtada S, Lester ER, Khursigara G, Molloy L, Carpenter TO, Braddock DT. Musculoskeletal Comorbidities and Quality of Life in ENPP1‐Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models. Journal Of Bone And Mineral Research 2020, 37: 494-504. PMID: 34882836, PMCID: PMC9667476, DOI: 10.1002/jbmr.4487.Peer-Reviewed Original ResearchConceptsENPP1 deficiencyAsj/Musculoskeletal complicationsBrief Pain Inventory-Short FormPhysical Function Short FormFibroblast growth factor 23Achilles tendon calcificationHealth-related qualityMajority of patientsGrowth factor 23Cervical spine fusionPresence of enthesopathyQuality of lifeAnalgesic medicationRegular chowResidual painAdult patientsDose escalationFactor 23Replacement therapyPhysical functionCardiovascular calcificationTendon calcificationAchilles tendonSpine fusionUnraveling the mechanism of recognition of the 3’ splice site of the adenovirus major late promoter intron by the alternative splicing factor PUF60
Hsiao HT, Crichlow GV, Murphy JW, Folta-Stogniew EJ, Lolis EJ, Braddock DT. Unraveling the mechanism of recognition of the 3’ splice site of the adenovirus major late promoter intron by the alternative splicing factor PUF60. PLOS ONE 2020, 15: e0242725. PMID: 33253191, PMCID: PMC7703929, DOI: 10.1371/journal.pone.0242725.Peer-Reviewed Original ResearchImproving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT. Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering. Clinical And Translational Science 2020, 14: 362-372. PMID: 33064927, PMCID: PMC7877847, DOI: 10.1111/cts.12887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveDisease Models, AnimalEnzyme Replacement TherapyGlycosylationHalf-LifeHistocompatibility Antigens Class IHumansMaleMice, TransgenicPhosphoric Diester HydrolasesProtein EngineeringProtein Structure, TertiaryPyrophosphatasesReceptors, FcRecombinant Fusion ProteinsVascular CalcificationConceptsProtein engineeringO-BuN-glycansGlycosylation engineeringCellular recyclingENPP1-deficient miceTerminal sialylationBiomanufacturing platformProtein therapeuticsCalcification disordersSialylationCellsVivo activityFc neonatal receptorTherapeuticsArterial calcificationProteinMurine modelManNAcEnzyme replacementNeonatal receptorEfficacious levelsGeneral strategyThree-prong strategyDrug potency
2019
Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations
Kotwal A, Ferrer A, Kumar R, Singh RJ, Murthy V, Schultz-Rogers L, Zimmermann M, Lanpher B, Zimmerman K, Stabach PR, Klee E, Braddock DT, Wermers RA. Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations. Journal Of Bone And Mineral Research 2019, 35: 662-670. PMID: 31826312, PMCID: PMC7771569, DOI: 10.1002/jbmr.3938.Peer-Reviewed Original ResearchConceptsAutosomal recessive hypophosphatemic rickets type 2Biallelic mutationsMonoallelic mutationsPrimary hyperparathyroidismPathogenic variantsCarotid intima-media thicknessClassic disease manifestationsNormocalcemic primary hyperparathyroidismC-terminal FGF23Intima-media thicknessWhole-exome sequencingClinical findingsArterial calcificationPeriarticular calcificationSpectrum of phenotypesIntact FGF23Disease manifestationsBilateral femursENPP1 variantsBone deformitiesBiochemical manifestationsType 2ENPP1 geneExome sequencingHyperparathyroidismHuman Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency
Oheim R, Zimmerman K, Maulding ND, Stürznickel J, von Kroge S, Kavanagh D, Stabach PR, Kornak U, Tommasini SM, Horowitz MC, Amling M, Thompson D, Schinke T, Busse B, Carpenter TO, Braddock DT. Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency. Journal Of Bone And Mineral Research 2019, 35: 528-539. PMID: 31805212, PMCID: PMC7184798, DOI: 10.1002/jbmr.3911.Peer-Reviewed Original ResearchConceptsAutosomal recessive hypophosphatemic rickets type 2ENPP1 deficiencyEarly-onset osteoporosisGene-dose effectOnset osteoporosisAsj/Bone mineral density scansBone mineralization disturbancesRenal phosphate wastingCortical boneDose effectMild osteomalaciaMineralization disturbancesFGF23 levelsMild elevationPlasma FGF23Arterial calcificationBone massPhosphate wastingSkeletal manifestationsBone fragilityThoracic spineWild-type family membersType 2Adult menExtraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome
Gordon C, Cleveland R, Baltrusaitis K, Massaro J, D'Agostino R, Liang M, Snyder B, Walters M, Li X, Braddock D, Kleinman M, Kieran M, Gordon L. Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome. Bone 2019, 125: 103-111. PMID: 31077852, PMCID: PMC6628204, DOI: 10.1016/j.bone.2019.05.008.Peer-Reviewed Original ResearchConceptsUrinary calcium/creatinine ratioCalcium/creatinine ratioExtraskeletal calcificationParathyroid hormoneClinical trialsHutchinson-Gilford progeria syndromeCreatinine ratioPhysical examinationNormal limitsPlasma magnesiumFibroblast growth factor 23Successive clinical trialsNormal renal functionCalcium carbonate supplementationGrowth factor 23Age-matched controlsEvaluable patientsRoutine supplementationSupplement discontinuationZoledronate therapyRenal functionCalcinosis cutisCalcium supplementationFactor 23Serum calcium
2017
Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice
Caballero D, Li Y, Fetene J, Ponsetto J, Chen A, Zhu C, Braddock DT, Bergwitz C. Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice. PLOS ONE 2017, 12: e0180098. PMID: 28704395, PMCID: PMC5509111, DOI: 10.1371/journal.pone.0180098.Peer-Reviewed Original ResearchConceptsRenal calcificationCompared to WT miceElevated urinary excretionRenal stone diseaseNucleotide pyrophosphatase phosphodiesterase 1WT miceDietary calciumUrinary excretionIntraperitoneal administrationStone diseaseNull miceMouse mutationMiceCalcificationNephrocalcinosisNpt2aDisordersUnrecognized factorsContribution of genotypePresent studyPhosphodiesterase 1PPINpt2cPatientsNephrolithiasis
2016
In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery
Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, López-Giráldez F, Ricciardi A, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock DT, Mark Saltzman W, Ly DH, Glazer PM. In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery. Nature Communications 2016, 7: 13304. PMID: 27782131, PMCID: PMC5095181, DOI: 10.1038/ncomms13304.Peer-Reviewed Original ResearchConceptsNanoparticle deliveryGene correctionReversal of splenomegalyPeptide nucleic acidLow off-target effectsVivo correctionGenome editingOff-target effectsGene editingHaematopoietic stem cellsNucleic acidsDonor DNAStem cellsΓPNAΒ-thalassaemiaNanoparticlesDeliveryEditingSCF treatmentTriplex formation
2015
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy
Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, Covo MS, Tehan M, Yang G, Cheng Z, Bouchard K, Yu ZX, Thorn S, Wang X, Folta-Stogniew EJ, Negrete A, Sinusas AJ, Shiloach J, Zubal G, Madri JA, De La Cruz EM, Braddock DT. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nature Communications 2015, 6: 10006. PMID: 26624227, PMCID: PMC4686714, DOI: 10.1038/ncomms10006.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseVascular calcificationArterial calcificationOrphan diseaseCommon diseaseSequelae of diseaseEctopic vascular calcificationInternal elastic laminaPrevent mortalityRenal failureCardiac failureKidney diseaseSubcutaneous administrationRodent modelsAnimal modelsEctopic calcificationVascular wallLarge arteriesElastic laminaDiseaseCalcificationCalciphylaxisDecreased concentrationSclerosisArtery
2014
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014, 510: 542-546. PMID: 24847880, PMCID: PMC4074244, DOI: 10.1038/nature13270.Peer-Reviewed Original Research
2013
Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke*♦
Albright RA, Ornstein DL, Cao W, Chang WC, Robert D, Tehan M, Hoyer D, Liu L, Stabach P, Yang G, De La Cruz EM, Braddock DT. Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke*♦. Journal Of Biological Chemistry 2013, 289: 3294-3306. PMID: 24338010, PMCID: PMC3916532, DOI: 10.1074/jbc.m113.505867.Peer-Reviewed Original ResearchConceptsExtracellular membrane proteinsMembrane proteinsSubstrate specificityMolecular basisHigh-resolution crystal structuresResolution crystal structureComparative structural analysisATP hydrolysisNPP1Brain vascular endotheliumCorresponding regionTerminal phosphateLow nanomolar concentrationsPurinergic signalsPlatelet aggregationProteinATPEnzymeNanomolar concentrationsVascular endotheliumPhosphodiesterases 4Ap3AMetabolismSurface of chondrocytesTissue mineralizationDesmoplastic melanoma: A 12-year experience with sentinel lymph node biopsy
Broer PN, Walker ME, Goldberg C, Buonocore S, Braddock DT, Lazova R, Narayan D, Ariyan S. Desmoplastic melanoma: A 12-year experience with sentinel lymph node biopsy. European Journal Of Surgical Oncology 2013, 39: 681-685. PMID: 23522951, DOI: 10.1016/j.ejso.2013.02.025.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAgedAged, 80 and overBiopsy, NeedleDatabases, FactualDisease-Free SurvivalFemaleFollow-Up StudiesHumansImmunohistochemistryLymph NodesLymphatic MetastasisMaleMelanomaMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingProspective StudiesRisk AssessmentSentinel Lymph Node BiopsySkin NeoplasmsSurvival AnalysisTreatment OutcomeConceptsSentinel lymph node biopsyDesmoplastic melanomaMixed desmoplastic melanomasPure desmoplastic melanomaNodal metastasisDM subtypesSpecific melanoma subtypesAdditional positive nodesLymph node biopsyHigh incidence rateYale Melanoma UnitPaucity of dataPositive SLNCompletion lymphadenectomyPositive nodesDM groupNodal involvementNode biopsyRegional lymphSentinel lymphLocal recurrenceTransit recurrenceClinical outcomesDistant metastasisMelanoma Unit
2012
NPP4 is a procoagulant enzyme on the surface of vascular endothelium
Albright RA, Chang WC, Robert D, Ornstein DL, Cao W, Liu L, Redick ME, Young JI, De La Cruz EM, Braddock DT. NPP4 is a procoagulant enzyme on the surface of vascular endothelium. Blood 2012, 120: 4432-4440. PMID: 22995898, PMCID: PMC4017314, DOI: 10.1182/blood-2012-04-425215.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAdultAnimalsBlood CoagulationCoagulantsCyclic Nucleotide Phosphodiesterases, Type 4Dinucleoside PhosphatesEndothelium, VascularFluorescent Antibody TechniqueHumansHydrolysisIn Vitro TechniquesInsectaPhosphoric Diester HydrolasesPlatelet AggregationPyrophosphatasesTissue DistributionConceptsPlatelet dense granule componentsNucleotide pyrophosphatase/phosphodiesteraseRelease of ADPUncharacterized enzymesPyrophosphatase/phosphodiesteraseGranule componentsEnzymatic basisRapid disaggregationDense granule releasePlatelet aggregationExtracellular spaceAp3AConcentration-dependent mannerEnzymeGranule releaseVascular endotheliumADPProcoagulant enzymeADP receptorActivationAggregationMutants